The authors would like to apologize for an error in Figure 1D of their article.The methylation entropy for the methylation pattern shown in Figure 1D should read 'ME = 0.25' not 'ME = 0.1875'.The corrected figure appears below.The entropy for code bit (e) in Figure 1A is 3.321928095.
The objective of this study was to evaluate the use of the Kowa HA-2 applanation tonometer in measuring intraocular pressure (IOP) in dogs. Twenty eyes were used in an ex vivo study in which the calibration curve for manometry vs. tonometry was determined by artificially raising the IOP in 5 mmHg increments up to 60 mmHg (10-60 mmHg). Both eyes of 10 anesthetized dogs were studied in vivo to compare manometry vs. tonometry. In the ambulatory study, 168 healthy eyes, 74 eyes with glaucoma and 60 eyes with uveitis were evaluated by tonometry, which was performed with topical anesthesia and 1% fluorescein eye drops for the formation of fluorescein semicircles. The ex vivo study showed an excellent correlation coefficient (r2= 0.993) between the aneroid manometer and the Kowa HA-2 tonometer. In the in vivo study, there was no significant difference (P>0.05) between the IOP values by manometry and tonometry, showing the excellent accuracy of the Kowa HA-2 tonometer. In the ambulatory study using the Kowa HA-2 tonometer, the IOP values (mean±SD, in mmHg) were 15.1±1.8 (12.0 – 20.0) for the healthy eyes, 25.2±4.0 (20.0 – 38.0) for glaucomatous eyes and 10.1±2.3 (5.0 – 13.7) for eyes with uveitis. There was a strong correlation between the IOP values obtained by direct ocular manometry and those from the Kowa HA-2 tonometer. In the ambulatory study, the IOP values measured by the tonometer were compatible for healthy eyes and for eyes with glaucoma or uveitis. We conclude that Kowa HA-2 applanation tonometer is accurate and practical for IOP measurement in dogs.
The purpose of this study was to evaluate changes in the conjunctival and nasal microbiota, in the long term, of dogs undergoing bilateral dacryocystorhinostomy. Twelve male and female dogs (23 eyes), aged between 1 and 10 years, were enrolled in the study, selected on the basis of presentation with epiphora and chromodacryorrhea for at least six months. Cultures of material obtained from the ocular conjunctiva and nasal sinus of all dogs were evaluated to determine the conjunctival and nasal microbiota pre-and postoperatively (at 60, 120, and 240 d). Preoperatively, gram-negative bacteria were identified in the conjunctival microbiota of 66.5% (n=8), while gram-positive bacteria were found in 33.3% (n=4). Throughout the clinical evolution, a balance was found between the presence of gram-positive and gram-negative bacteria in the conjunctival microbiota. Pure cultures of Pseudomonas aeruginosa (25%) and Staphylococcus intermedius (25%) were found most frequently. Regarding the conjunctival microbiota, we can conclude that in obstructive diseases, there is a predominance of gram-negative bacteria in the lacrimal system, notably Pseudomonas aeruginosa. This study did not observe an increase in bacterial counts in the nasal cavity through the new surgical pathway to the conjunctival sac.
The effects of metaraminol bitartrate on intraocular pressure (IOP) were studied in dogs anesthetized with halothane. Forty-five healthy, adult, mixed-breed dogs, of both sexes, were divided into three groups of 15 dogs each (GI, GII and GIII) and maintained under general anesthesia with halothane after tranquilization with levomepromazine and induction with thiopental. Saline (0.9%) was administered intravenously (IV) to GI through continuous infusion, at a velocity of 0.125 mL kg-1 min-1. GII and GIII received metaraminol 0.004% IV, at a dose of 5 &mgr;g kg-1 min-1, at 0.125 mL kg-1 min-1 and at a dose of 2 &mgr;g kg-1 min-1, at 0.06 mL kg-1 min-1, respectively. IOP was measured by applanation tonometry (Tono-Pen) before and during anesthesia. Results showed that IOP decreased in GI, increased in GII, and remained at basal levels in GIII. Continuous infusion of metaraminol at 2 &mgr;g kg min-1 maintained IOP at pretest levels, while infusion at 5 &mgr;g kg-1 min-1 produced an elevation of IOP.
In this study, derived complex carcinoma (CC) and simple carcinoma (SC) cell lines were established and cultured under two-dimensional (2D) and three-dimensional (3D) conditions. The 3D was performed in six-well AlgiMatrix™ (LifeTechnologies®, Carlsbad, CA, USA) scaffolds, resulting in spheroids sized 50-125 µm for CC and 175-200 µm for SC. Cell viability was demonstrated up to 14 days for both models. Epidermal growth factor receptor (EGFR) was expressed in CC and SC in both systems. However, higher mRNA and protein levels were observed in SC 2D and 3D systems when compared with CC (P < 0.005). The connective tissue modulators, metalloproteinases-1, -2, -9 and -13 (MMPs), relaxin receptors 1 and 2 (RXR1 and RXR2) and E-cadherin (CDH1) were quantitated. All were upregulated similarly when canine mammary tumour (CMT)-derived cell lines were cultured under 3D AlgiMatrix, except CDH1 that was downregulated (P < 0.005). These results are promising towards the used of 3D system to increase a high throughput in vitro canine tumour model.
Epigenetic and chromatin modifications play particularly important roles in embryonic and induced pluripotent stem cells (ESCs and iPSCs) allowing for the cells to both differentiate and dedifferentiate back to a pluripotent state. We analyzed how the loss of a key chromatin-modifying enzyme, histone deacetylase 1 (HDAC1), affects early and cardiovascular differentiation of both ESCs and iPSCs. We also investigated potential differences between these two cell types when differentiation is induced. Our data indicate an essential role for HDAC1 in deacetylating regulatory regions of key pluripotency-associated genes during early differentiation. Although HDAC1 functions primarily as a HDAC, its loss also affects DNA methylation in ESCs and iPSCs both during pluripotency and differentiation. We show that HDAC1 plays a crucial, nonredundant role in cardiomyocyte differentiation and maturation. Our data also elucidate important differences between ESCs and iPSCs, when levels of this enzyme are reduced, that affect their ability to differentiate into functional cardiomyocytes. As varying levels of chromatin-modifying enzymes are likely to exist in patient-derived iPSCs, understanding the molecular circuitry of these enzymes in ESCs and iPSCs is critical for their potential use in cardiovascular therapeutic applications
Canine transmissible venereal tumour (CTVT) is a neoplasm transmitted among healthy dogs by direct contact with injured skin and/or mucous tissue. This study aimed to identify the TP53 gene, messenger RNA (mRNA) as well as the expression of p53, Bcl‐2 and p63 proteins in histological sections of 13 CTVT samples at different stages of evolution. The in situ hybridization (ISH) and in situ reverse transcriptase polymerase chain reaction (RT‐PCR) assays were used, which showed the DNA homologous to TP53 and its respective mRNA in 92.3% of the samples. We detected p53, p63 and Bcl‐2 proteins in most of the cell samples in different grades of intensity. In addition, 46% of the samples were in the progressive and 54% in the regression phase. This is the first description of these proteins and a detailed study of their role in CTVT cells needs to be addressed in or to verify how these cells undergo apoptosis.
Background: Episcleral inflammation may be assumed to be primary immune-mediated, secondary to intra-or extraocular diseases, or systemic abnormalities. We aimed to report a confirmed and another suspect case of nodular episclerokeratites (NEK) due to its rarity in the clinical setting and the paucity of case reports in Brazilian literature. Cases: Case 1. Refers to a 7-year-old castrated male, Collie-mixed breed, presenting with epiphora and an irregular ocular surface shape in the left eye (LE). Ophthalmic evaluation of this eye revealed mucoid discharge, conjunctival hyperemia, episcleral injection, and a gelatinous mass in the temporal limbic region. Biomicroscopic evaluation of the anterior chamber, lens, and vitreous was impaired in the LE because of corneal vessels and a mild flare in the aqueous humor. Histopathology of a scleral biopsy revealed the presence of lymphocytes, histiocytes, and some plasma cells. Positive CD3-lymphocytes were observed by immunohistochemistry, confirming the diagnosis of NEK. Case 2. Refers to a 8-year-old, spayed female Border Collie with a history of exophthalmos, conjunctival hyperemia, and inability to close the eyelid of the LE. During ophthalmic examination, an irregular espicleral nodule of approximately 9 mm was also found in the temporal limbic region, along with enlargement of episcleral vessels and scleral thinning at the equatorial region. The cornea showed mild and diffuse edema, and white crystal-like deposits were distributed in a band-like fashion at the dorsal aspect. Ultrasonography revealed scleral thinning without evidence of a mass effect arising from the iris, ciliary body, or retrobulbar space. Based on these findings, NEK was suspected. In both cases, the clinical signs reduced significantly after seven days of topical treatment with corticosteroids and cyclosporine. Discussion: It is assumed that scleral disorders are primarily immune mediated. However, such conditions may develop secondary to ocular trauma (surgery and foreign bodies), Ehrlichia canis, and Onchocerca spp. Infections and situations were ruled out in both cases. In case 1, additional histological and immunohistochemical findings supported a primary and immune-mediated scleral disease. Although the definitive diagnosis was not confirmed by histology in case 2, one can assume that the episcleral inflammation may have arisen due to an immune-mediated disorder once the eye responded positively to corticosteroid therapy. Additionally, secondary glaucoma was excluded as a possible diagnosis in case 2, because the intraocular pressure of the affected eye was below the reference range for dogs, coupled with the irregular appearance of the episclera, which is not characteristic of canine glaucoma. However, in case 2, because remission of the masses of neoplastic origin after corticotherapy was not expected, the tumor was discarded. NEK has a characteristic ploriferative behavior and resistance to topical immunosuppression; clinical recurrence was not observed in the LE of either patient who remained on treatment after 60 days of follow-up. Regarding prognosis, one study showed a correlation between cellular contingent and therapeutic responses. The percentage of positive CD79a cells (B-lymphocytes) was significantly higher in cases of epicleritis and NEK, in which a poor response was achieved after topical immunosuppressive treatment. As shown by the veterinary literature and the cases described here, the complete remission of NEK is more common in unilateral cases, as confirmed after a 12-month follow-up. The 2 reported cases are useful for clarifying the common findings, diagnosis, and long-term management of NEK. Scleral abnormalities, such as NEK, must be included in the list of differential diagnoses of glaucoma, neoplasia, and endophthalmitis during medical examination. Keywords: keratitis, uveitis, neoplasia, immunosuppression, dog. Título: Episcleroceratite nodular granulomatosa em cães Descritores: ceratite, uveíte, neoplasia, imunossupressão, cão.
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